This invention relates to compounds having fungicidal activity.
In a first aspect the invention provides the use of a compound of general formula I, complexes and salts thereof as phytopathogenic fungicides 
where
A1 is a 2-pyridyl or its N-oxide, each of which may be substituted by up to four groups at least one of which is haloalkyl;
Y is a formula (D) or (E):
xe2x80x94Lxe2x80x94A2xe2x80x94
xe2x80x94L1xe2x80x94A3xe2x80x94xe2x80x83xe2x80x83(E)
A2 is heterocyclyl or carbocyclyl, each of which may be substituted;
A3 is heterocyclyl or carbocyclyl, each of which may be substituted, or acyl;
L is a 3-atom linker, selected from the list: xe2x80x94N(R5)C(xe2x95x90X)N(R6)xe2x80x94, xe2x80x94N(R5)C(xe2x95x90X)CH(R3)xe2x80x94, xe2x80x94CH(R3)N(R5)CH(R4)xe2x80x94, xe2x80x94CH(R3)N(R5)C(xe2x95x90X)xe2x80x94, xe2x80x94N(R3)CH(R4)C(xe2x95x90X)xe2x80x94 and xe2x80x94Oxe2x80x94N(R5)C(xe2x95x90X)xe2x80x94; wherein A1 is attached to the left hand side of linker L;
L1 is a 4-atom linker selected from the list: xe2x80x94N(R9)C(xe2x95x90X)xe2x80x94X1xe2x80x94CH(R7)xe2x80x94, xe2x80x94N(R9)C(xe2x95x90X)CH(R7)CH(R8)xe2x80x94, xe2x80x94N(R9)C(xe2x95x90X)C(R7)xe2x95x90C(R8)xe2x80x94, xe2x80x94N(R9)C(R7)xe2x95x90C(R8)xe2x80x94C(xe2x95x90X)xe2x80x94, xe2x80x94N(R9)C(R7)xe2x95x90C(R8)xe2x80x94SO2xe2x80x94, xe2x80x94N(R9)C(xe2x95x90X)C(R7)(R8)xe2x80x94SO2xe2x80x94 and xe2x80x94N(R9)C(xe2x95x90X)C(R7)(R8)xe2x80x94X1xe2x80x94; wherein A1 is attached to the left hand side of linker L1;
R1, R2, R3, R4, R7 and R8, which may be the same or different, are Rb, cyano, nitro, halogen, xe2x80x94ORb, xe2x80x94SRb or optionally substituted amino;
R5 and R6 which may be the same or different, are Rb, cyano or nitro; or any R1, R3 or R5 group, together with the interconnecting atoms, can form a 3-, 4-, 5- or 6-membered ring with any R2, R4 or R6 or any R1, R2, R3, R4, R5 or R6 group, together with the interconnecting atoms can form a 5- or 6-membered ring with A2;
or R1 or R2, or R7 or R8, together with the interconnecting atoms, may form a 3-, 4-, 5- or 6-membered ring, which may be substituted;
Rb is alkyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl, each of which may be substituted, or hydrogen or acyl;
X is oxygen or sulfur;
X1 is oxygen, sulfur or xe2x80x94N(R9)xe2x80x94, and
R9 is Rb, cyano or nitro, or R9 and A3, R1, R2, R7 and R8, together with the interconnecting atoms, may form a 3-, 4-, 5- or 6-membered ring, which may be substituted.
Preferred substituents on the 2-pyridyl group (A1) are halogen, hydroxy, cyano, nitro, SF5, trialkylsilyl, optionally substituted amino, acyl, or a group xe2x80x94Ra, xe2x80x94ORa or xe2x80x94SRa, or a group xe2x80x94C(Ra)xe2x95x90Nxe2x80x94Q, where Q is xe2x80x94Ra, xe2x80x94ORa, xe2x80x94SRa or optionally substituted amino, wherein Ra is alkyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl, each of which may be substituted; or two adjacent substituents together with the atoms to which they are attached form an optionally substituted ring which can contain up to 3 hetero atoms. Preferably, the 2-pyridyl group is substituted at the 3 and/or 5 position.
Preferred compounds are those in which one or more of the following features are present:
A2 is optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted cyclohexyl or optionally substituted cyclopropyl; or
A3 is optionally substituted phenyl, optionally substituted heterocyclyl or acyl; or
R1, R2, R3, R4, R7 and R8 are hydrogen, optionally substituted alkyl, optionally substituted phenyl, cyano, acyl or halogen (more preferably R1 and R2 are hydrogen); or
R5 and R6 are hydrogen, optionally substituted alkyl or acyl; or
R7 and R8 are hydrogen, optionally substituted alkyl or acyl; or
R9 is hydrogen or optionally substituted alkyl; or
the 2-pyridyl group (A1) is substituted by alkoxy, alkyl, cyano, halogen, nitro, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl or trifluoromethyl, (preferably chlorine or trifluoromethyl).
Many of the compounds of formula I are novel. Therefore, according to a further aspect, the invention provides compounds of formula I where:
Y is xe2x80x94Lxe2x80x94A2xe2x80x94 and;
L is xe2x80x94NHC(xe2x95x90X)NHxe2x80x94; and
A2 is phenyl optionally substituted by halogen, haloalkyl, phenoxy, alkoxy, alkyl, CN, NO2, SO2xe2x80x94(N-tetrahydropyridinyl), alkylthio, acyl, phenylsulphonyl, dialkylamino, alkylsulphonyl, benzylsulphonyl, S(phenyl substituted by halogen); or
A2 is cycloalkyl; or naphthyl optionally substituted by NO2; or
L is xe2x80x94NHC(xe2x95x90O)CH(R3)xe2x80x94;
R3 is hydrogen, alkyl, phenyl, halogen or acyloxy;
A2 is phenyl optionally substituted by halogen, NO2 or alkoxy; or thienyl; or imidazolyl; or pyrrolinyl substituted by alkoxy; or
L is xe2x80x94CH(R3)N(R5)CH2xe2x80x94;
R3 is N-alkylcarbamoyl or akoxycarbonyl;
R5 is hydrogen or acyl;
A2 is phenyl optionally substituted by alkyl, alkoxy, halogen, NO2, haloalkyl or phenoxy; or is naphthyl; or
L is xe2x80x94CH(R3)NHC(xe2x95x90O)xe2x80x94;
R3 is N-alkylcarbamoyl or alkoxycarbonyl;
A2 is phenyl optionally substituted by alkoxy, halogen, NO2, haloalkyl, phenoxy or phenyl; or is cycloalkyl; or
L is xe2x80x94Oxe2x80x94NHC(xe2x95x90O)xe2x80x94 and A2 is phenyl substituted by alkyl; or
Y is xe2x80x94L1xe2x80x94A3xe2x80x94 and;
L1 is xe2x80x94NHC(xe2x95x90O)(CH2)2xe2x80x94, and A3 is phenyl substituted by alkyl; or
L1 is xe2x80x94NHC(xe2x95x90S)NHCH2xe2x80x94, and A3 is phenyl; or
L1 is xe2x80x94NHC(xe2x95x90O)CH(alkyl)Sxe2x80x94, and A3 is phenyl; or
L1 is xe2x80x94NHC(xe2x95x90O)OCH2xe2x80x94, xe2x80x94NHC(xe2x95x90O)(CH2)2xe2x80x94, xe2x80x94NHC(xe2x95x90O)NHCH2xe2x80x94, xe2x80x94NHC(xe2x95x90S)NHCH2xe2x80x94, xe2x80x94N(alkyl)C(xe2x95x90O)CH2Oxe2x80x94 or xe2x80x94NHC(xe2x95x90O)CH2Oxe2x80x94;
R1 is hydrogen;
R2 is hydrogen or alkoxycarbonyl;
A3 is phenyl optionally substituted by halogen, alkyl, phenyl, OH, alkoxy or alkoxycarbonyl; or fluorenyl; or pyridyl optionally substituted by halogen or haloalkyl; or thiadiazolyl substituted by alkyl; or benzthiazolyl optionally substituted by halogen or by phenyl substituted by halogen; or quinolinyl substituted by haloalkyl; or triazolyl substituted by alkyl or phenyl; or tetrazolyl substituted by alkyl or cycloalkyl; or pyrimidinyl substituted by alkyl; or benzoxazolyl; or imidazolyl substituted by alkyl; or thiazolinyl substituted by alkyl and methylene; or
L1 is xe2x80x94NHC(xe2x95x90O)CH(R8)N(R9)xe2x80x94;
R1 is hydrogen;
R2 is hydrogen or alkyl;
R8 and R9 are each hydrogen or alkyl;
A3 is benzoyl optionally substituted by alkyl; or benzyloxycarbonyl; or alkoxycarbonyl; or
L1 is xe2x80x94NHC(xe2x95x90O)CH(alkyl)SO2xe2x80x94;
R1 and R2 are each hydrogen;
A3 is phenyl; or
L1 is xe2x80x94NHC(xe2x95x90O)CH2X1xe2x80x94, where X1 and A3 form a 2-oxo-N-benzthiazolyl ring which is substituted by halogen; and
R1 and R2 are each hydrogen.
The invention also includes any of the compounds specifically exemplified hereinafter.
Any alkyl group may be straight or branched and is preferably of 1 to 10 carbon atoms, especially 1 to 7 and particularly 1 to 5 carbon atoms.
Any alkenyl or alkynyl group may be straight or branched and is preferably of 2 to 7 carbon atoms and may contain up to 3 double or triple bonds which may be conjugated, for example vinyl, allyl, butadienyl or propargyl.
Any carbocyclyl group may be saturated, unsaturated or aromatic, and contain 3 to 8 ring-atoms. Preferred saturated carbocyclyl groups are cyclopropyl, cyclopentyl or cyclohexyl. Preferred unsaturated carbocyclyl groups contain up to 3 double bonds. A preferred aromatic carbocyclyl group is phenyl. The term carbocylic should be similarly construed. In addition, the term carbocyclyl includes any fused combination of carbocyclyl groups, for example naphthyl, phenanthryl, indanyl and indenyl.
Any heterocyclyl group may be saturated, unsaturated or aromatic, and contain 5 to 7 ring-atoms up to 4 of which may be hetero-atoms such as nitrogen, oxygen and sulfur. Examples of heterocyclyl groups are furyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, dioxolanyl, oxazolyl, thiazolyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyranyl, pyridyl, piperidinyl, dioxanyl, morpholino, dithianyl, thiomorpholino, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, sulfolanyl, tetrazolyl, triazinyl, azepinyl, oxazepinyl, thiazepinyl, diazepinyl and thiazolinyl. In addition, the term heterocyclyl includes fused heterocyclyl groups, for example benzimidazolyl, benzoxazolyl, imidazopyridinyl, benzoxazinyl, benzothiazinyl, oxazolopyridinyl, benzofuranyl, quinolinyl, quinazolinyl, quinoxalinyl, dihydroquinazolinyl, benzothiazolyl, phthalimido, benzofuranyl, benzodiazepinyl, indolyl and isoindolyl. The term heterocyclic should be similarly construed.
Any alkyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl group, when substituted, may be substituted by one or more substituents, which may be the same or different, and may be selected from the list: hydroxy; mercapto; azido; nitro; halogen; cyano; acyl; optionally substituted amino; optionally substituted carbocyclyl; optionally substituted heterocyclyl; cyanato; thiocyanato; xe2x80x94SF5; xe2x80x94ORa; xe2x80x94SRa and xe2x80x94Si(Ra)3, where Ra is alkyl, alkenyl, alkynyl, carbocyclyl and heterocyclyl, each of which may be substituted. In the case of any carbocyclyl or heterocyclyl group the list includes additionally: alkyl, alkenyl and alkynyl, each of which may be substituted. Preferred substituents on any alkyl, alkenyl or alkynyl group are alkoxy, haloalkoxy or alkylthio, each containing 1 to 5 carbon atoms; halogen; or optionally substituted phenyl. Preferred substituents on any carbocyclyl or heterocyclyl group are alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio, each containing 1 to 5 carbon atoms; halogen; or optionally substituted phenyl.
In the case of any alkyl group or any unsaturated ring-carbon in any carbocyclyl or heterocyclyl group the list includes a divalent group such as oxo or imino, which may be substituted by optionally substituted amino, Ra or xe2x80x94ORa. Preferred groups are oxo, imino, alkylimino, oximino, alkyloximino or hydrazono.
Any amino group, when substituted and where appropriate, may be substituted by one or two substituents which may be the same or different, selected from the list: optionally substituted alkyl, optionally substituted amino, xe2x80x94ORa and acyl groups. Alternatively two substituents together with the nitrogen to which they are attached may form a heterocyclyl group, preferably a 5 to 7-membered heterocyclyl group, which may be substituted and may contain other hetero atoms, for example morpholino, thiomorpholino or piperidinyl.
The term acyl includes the residues of sulfur and phosphorus-containing acids as well as carboxylic acids. Typically the residues are covered by the general formulae xe2x80x94C(xe2x95x90Xa)Rc, xe2x80x94S(O)pRc and xe2x80x94P(xe2x95x90Xa)(ORa)(ORa), where appropriate Xa is O or S, Rc is as defined for Ra, xe2x80x94ORa, xe2x80x94SRa optionally substituted amino or acyl; and p is 1 or 2. Preferred groups are xe2x80x94C(xe2x95x90O)Rd, xe2x80x94C(xe2x95x90S)Rd, and xe2x80x94S(O)pRd where Rd is alkyl, C1 to C5 alkoxy, C1 to C5 alkylthio, phenyl, heterocyclyl or amino, each of which may be substituted.
By the term xe2x80x9csaltsxe2x80x9d is meant salts the cations or anions of which are known and accepted in the art for the formation of salts for agricultural or horticultural use. Suitable salts with bases include alkali metal (e.g. sodium and potassium), alkaline earth metal (e.g. calcium and magnesium), ammonium and amine (e.g. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts. Suitable acid addition salts, e.g. formed by compounds of formula I containing an amino group, include salts with inorganic acids, for example hydrochlorides, sulphates, phosphates and nitrates and salts with organic acids for example acetic acid.
Complexes of compounds of the invention are usually formed from a salt of formula MAn2, in which M is a divalent metal cation, e.g. copper, manganese, cobalt, nickel, iron or zinc and An is an anion, e.g. chloride, nitrate or sulfate.
In cases where the compounds of the invention exist as the E and Z isomers, the invention includes individual isomers as well as mixtures thereof.
In cases where compounds of the invention exist as tautomeric isomers, the invention includes individual tautomers as well as mixtures thereof.
In cases where the compounds of the invention exist as optical isomers (for example where R1 and R2 are different), the invention includes individual isomers as well as mixtures thereof.
The compounds of the invention have activity as fungicides, especially against fungal diseases of plants, e.g. mildews and particularly cereal powdery mildew (Erysiphe graminis) and vine downy mildew (Plasmopara viticola), rice blast (Pyricularia oryzae), cereal eyespot (Pseudocercosporella herpotrichoides), rice sheath blight (Pellicularia sasakii), grey mould (Botrytis cinerea), damping off (Rhizoctonia solani), wheat brown rust (Puccinia recondita), late tomato or potato blight (Phytophthora infestans), apple scab (Venturia inaequalis), and glume blotch (Leptosphaeria nodorum). Other fungi against which the compounds may be active include other powdery mildews, other rusts, and other general pathogens of Deuteromycete, Ascomycete, Phycomycete and Basidomycete origin.
The invention thus also provides a method of combating fungal pests such as phytopathogenic fungi at a locus infested or liable to be infested therewith, which comprises applying to the locus a compound of formula I or a complex or salt thereof.
The invention also provides an agricultural composition comprising a compound of formula I or a complex or salt thereof in admixture with an agriculturally acceptable diluent or carrier.
The composition of the invention may of course include more than one compound of the invention.
In addition, the composition can comprise one or more additional active ingredients, for example compounds known to possess plant-growth regulant, herbicidal, fungicidal, insecticidal, acaricidal, antimicrobial or antibacterial properties. Alternatively the compound of the invention can be used in sequence with the other active ingredient.
The diluent or carrier in the composition of the invention can be a solid or a liquid optionally in association with a surface-active agent, for example a dispersing agent, emulsifying agent or wetting agent. Suitable surface-active agents include anionic compounds such as a carboxylate, for example a metal carboxylate of a long chain fatty acid; an N-acylsarcosinate; mono- or di-esters of phosphoric acid with fatty alcohol ethoxylates or alkyl phenol ethoxylates or salts of such esters; fatty alcohol sulfates such as sodium dodecyl sulfate, sodium octadecyl sulfate or sodium cetyl sulfate; ethoxylated fatty alcohol sulfates; ethoxylated alkylphenol sulfates; lignin sulfonates; petroleum sulfonates; alkyl-aryl sulfonates such as alkyl-benzene sulfonates or lower alkylnaphthalene sulfonates, e.g. butyl-naphthalene sulfonate; salts of sulfonated naphthalene-formaldehyde condensates; salts of sulfonated phenol-formaldehyde condensates; or more complex sulfonates such as the amide sulfonates, e.g. the sulfonated condensation product of oleic acid and N-methyl taurine; the dialkyl sulfosuccinates, e.g. the sodium sulfonate of dioctyl succinate; acid derivatives of alkyl glycosides and alkylpolyglycosides materials and their metal salts, e.g. alkyl polyglycoside citrate or tartrate materials; or mono-, di- and tri-alkyl esters of citric acid and their metal salts.
Nonionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid amides or fatty-alkyl- or alkenyl-substituted phenols with ethylene and/or propylene oxide; fatty esters of polyhydric alcohol ethers, e.g. sorbitan fatty acid esters; condensation products of such esters with ethylene oxide, e.g. polyoxyethylene sorbitan fatty acid esters; alkyl glycosides, alkyl polyglycoside materials; block copolymers of ethylene oxide and propylene oxide; acetylenic glycols such as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, ethoxylated acetylenic glycols; acrylic based graft copolymers; alkoxylated siloxane surfactants; or imidazoline type surfactants, e.g. 1-hydroxyethyl-2-alkylimidazoline.
Examples of a cationic surface-active agent include, for instance, an aliphatic mono-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen-containing amine such as an amine oxide, polyoxyethylene alkylamine or polyoxypropylene alkylamine; an amide-linked amine prepared by the condensation of a carboxylic acid with a di- or polyamine; or a quaternary ammonium salt.
The compositions of the invention can take any form known in the art for the formulation of agrochemicals, for example, a solution, an aerosol, a dispersion, an aqueous emulsion, a microemulsion, a dispersible concentrate, a dusting powder, a seed dressing, a fumigant, a smoke, a dispersible powder, an emulsifiable concentrate, granules or an impregnated strip. Moreover it can be in a suitable form for direct application or as a concentrate or primary composition which requires dilution with a suitable quantity of water or other diluent before application.
A dispersible concentrate comprises a compound of the invention dissolved in one or more water miscible or semi-water miscible solvents together with one or more surface active and/or polymeric material. Addition of the formulation to water results in the crystallisation of the active ingredient, the process being controlled by the surfactants and/or polymers resulting in a fine dispersion.
A dusting powder comprises a compound of the invention intimately mixed and ground with a solid pulverulent diluent, for example, kaolin.
An emulsifiable concentrate comprises a compound of the invention dissolved in a water-immiscible solvent which forms an emulsion or miscroemulsion on addition to water in the presence of an emulsifying agent.
A granular solid comprises a compound of the invention associated with similar diluents to those that may be employed in dusting powders, but the mixture is granulated by known methods. Alternatively it comprises the active ingredient absorbed or coated on a pre-formed granular carrier, for example, Fuller""s earth, attapulgite, silica or limestone grit.
Wettable powders, granules or grains usually comprise the active ingredient in admixture with suitable surfactants and an inert powder diluent such as clay or diatomaceous earth.
Another suitable concentrate is a flowable suspension concentrate which is formed by grinding the compound with water or other liquid, surfactants and a suspending agent.
The concentration of the active ingredient in the composition of the present invention, as applied to plants is preferably within the range of 0.0001 to 1.0 percent by weight, especially 0.0001 to 0.01 percent by weight. In a primary composition, the amount of active ingredient can vary widely and can be, for example, from 5 to 95 percent by weight of the composition.
The invention is generally applied to seeds, plants or their habitat. Thus, the compound can be applied directly to the soil before, at or after drilling so that the presence of active compound in the soil can control the growth of fungi which may attack seeds. When the soil is treated directly the active compound can be applied in any manner which allows it to be intimately mixed with the soil such as by spraying, by broadcasting a solid form of granules, or by applying the active ingredient at the same time as drilling by inserting it in the same drill as the seeds. A suitable application rate is within the range of from 5 to 1000 g per hectare, more preferably from 10 to 500 g per hectare.
Alternatively the active compound can be applied directly to the plant by, for example, spraying or dusting either at the time when the fungus has begun to appear on the plant or before the appearance of fungus as a protective measure. In both such cases the preferred mode of application is by foliar spraying. It is generally important to obtain good control of fungi in the early stages of plant growth, as this is the time when the plant can be most severely damaged. The spray or dust can conveniently contain a pre- or post-emergence herbicide if this is thought necessary. Sometimes, it is practicable to treat the roots, bulbs, tubers or other vegetative propagule of a plant before or during planting, for example, by dipping the roots in a suitable liquid or solid composition. When the active compound is applied directly to the plant a suitable rate of application is from 0.025 to 5 kg per hectare, preferably from 0.05 to 1 kg per hectare.
In addition, the compounds of the invention can be applied to harvested fruits, vegetables or seeds to prevent infection during storage.
In addition, the compounds of the invention can be applied to plants or parts thereof which have been genetically modified to exhibit a trait such as fungal and/or herbicidal resistance.
In addition the compounds of the invention can be used to treat fungal infestations in timber and in public health applications.
Compounds of the invention may be prepared, in known manner, in a variety of ways. Such processes for the preparation of novel compounds of formula I constitute a feature of the invention.
Compounds of formula Ia, i.e. compounds of general formula I where Y is a formula (D) and L is xe2x80x94N(R5)C(xe2x95x90X)NHxe2x80x94, can be prepared by reacting compounds of formula II or their hydrochloride salts, with compounds of formula III according to reaction scheme 1. A preferred base is triethylamine. 
Compounds of formula Ib, i.e. compounds of general formula I where Y is of formula (D) and L is xe2x80x94N(R5)C(xe2x95x90O)CH(R3)xe2x80x94, may be prepared by reacting compounds of formula IV with compounds of formula II according to reaction scheme 2. A variety of methods are available to the chemist, for example, generation of the acid chloride of IV, using reagents such as phosphoryl chloride or oxalyl chloride, followed by addition of II. Alternatively, carbonyl diimidazole (CDI) can be used to activate compounds of formula IV prior to addition of II. 
Compounds of formula Ic and Id, i.e. compounds of general formula I where Y is of formula (D) and L is xe2x80x94CH(R3)xe2x80x94N(R5)xe2x80x94Wxe2x80x94 and W is xe2x80x94C(xe2x95x90X)xe2x80x94 or xe2x80x94CH(R4)xe2x80x94, wherein R3 is alkoxycarbonyl or carbamoyl respectively, can be prepared by various methods known to the skilled chemist. In particular, compounds of formula Ic or Id may be prepared from solid supported reagents of formula V according to reaction scheme 3, wherein the black circle represents Merrifield resin. 
Compounds of formula Ie, i.e. compounds of general formula I where Y is of formula (D) and L is xe2x80x94CH(R3)N(R5)C(xe2x95x90X)xe2x80x94 may be prepared by reacting compounds of formula VI with compounds of formula VII according to reaction scheme 4. 
Compounds of formula If, i.e. compounds of general formula I where Y is of formula (B) and L1 is xe2x80x94N(R9)C(xe2x95x90X)xe2x80x94L2xe2x80x94, where L2 is xe2x80x94CH(R7)CH(R8)xe2x80x94, xe2x80x94C(R8)(R7)xe2x80x94X1xe2x80x94 or xe2x80x94C(R7)xe2x95x90C(R8)xe2x80x94, may be prepared according to Scheme 5 by reacting compounds of formula VIII or their hydrochloride salts with compounds of formula IX in the presence of a base, where Q1 is a leaving group such as halogen, preferably chlorine. A preferred base is triethylamine. Compounds of formula IX can either be isolated or generated in situ. 
Compounds of formula Ig, i.e. compounds of general formula I where Y is of formula (E) and L1 is xe2x80x94N(R9)C(xe2x95x90X)xe2x80x94NHxe2x80x94CH(R7)xe2x80x94, may be prepared according to Scheme 6 by reacting compounds of formula VIII or their hydrochloride salts with compounds of formula X. A preferred base is triethylamine. 
Compounds of formula Ih, i.e. compounds of general formula I where Y is of formula (E) and L1 is xe2x80x94N(R9)C(xe2x95x90X)xe2x80x94C(R7)(R8)xe2x80x94X1xe2x80x94 wherein R7 and R8 are not both hydrogen and X is oxygen, may also be prepared according to Scheme 7 by reacting compounds of formula XI where Q1 is a leaving group, preferably bromine, with A2xe2x80x94X1xe2x80x94H in the presence of a suitable base, preferably potassium tert-butoxide. 
Compounds of formula Ii, i.e. compounds of general formula I where Y is of formula (E) and L1 is xe2x80x94N(R9)C(R7)xe2x95x90C(R8)xe2x80x94C(xe2x95x90X)xe2x80x94 wherein R7 is not hydrogen, may be prepared according to Scheme 8 by reacting compounds of formula VIII or their hydrochloride salts in the presence of a suitable base such as sodium acetate with compounds of formula XII. 
Compounds of formula Ij, i.e. compounds of general formula I where Y is of formula (E) and L1 is xe2x80x94N(R9)CHxe2x95x90C(R8)xe2x80x94C(xe2x95x90X)xe2x80x94, may be prepared according to Scheme 9 by reacting compounds of formula VIII or their hydrochloride salts in the presence of a suitable base such as sodium acetate with compounds of formula XIII. 
Compounds of formula Ik, i.e. compounds of general formula I where Y is of formula (E) and L1 is xe2x80x94N(R9)C(xe2x95x90X)Oxe2x80x94C(H)(R7)xe2x80x94, may be prepared according to Scheme 10 by reacting compounds of formula VIII or their hydrochloride salts in the presence of a suitable base such as triethylamine with compounds of formula XIV. 
Collections of compounds of formula (I) may also be prepared in a parallel manner, either manually, automatically or semi-automatically. This parallel preparation may be applied to the reaction procedure, work-up or purification of products or intermediates. For a review of such procedures see by S. H. DeWitt in xe2x80x9cAnnual Reports in Combinatorial Chemistry and Molecular Diversity: Automated synthesisxe2x80x9d, Volume 1, Verlag Escom 1997, pages 69 to 77.
Furthermore, compounds of the formula (I) may be prepared using solid-supported methods, where the reactants are bound to a synthetic resin. See for example: Barry A. Bunin in xe2x80x9cThe Combinatorial Indexxe2x80x9d, Academic Press, 1998 and xe2x80x9cThe tea-bag methodxe2x80x9d (Houghten, U.S. Pat. No. 4,631,211; Houghten et al., Proc. Natl. Acad. Sci. 1985, 82, 5131-5135).
The preparation of the processes described herein yields compounds of the formula (I) in the form of substance collections which are termed libraries. The present invention also relates to libraries which comprise at least two compounds of the formula (I).
Intermediates of formula V may be prepared in turn from compounds of formula XV, by methods analogous to that depicted in reaction scheme 11. Compounds of formula Va may be prepared by treating XV with a compound of formula XVI in the presence of a suitable base, such as triethylamine. Compounds of formula Vb may be prepared from compounds of formula XVa by treatment with compounds of formula XVII, sodium cyanoborohydride and acetic acid followed by reaction with compounds of formula XVIII and triethylamine. 
Compounds of formula XV can be prepared using similar methods to reaction scheme 12. 
Intermediates of formula VIII may be prepared by methods described in international application PCT/GB/99/00304.
Intermediates of formula IX can prepared from the corresponding carboxylic acid by methods known to the skilled chemist.
Intermediates of formula XI may be prepared according to Scheme 13 by reacting compounds of formula VIII in the presence of a suitable base such as triethylamine with compounds of formula XIX, in the presence of a carbonyl diimidazole (CDI). 
Other methods will be apparent to the chemist skilled in the art, as will be the methods for preparing starting materials and intermediates.